Biomimetic calcium phosphate coatings as bone morphogenetic protein delivery systems in spinal fusion

Abstract 

Background context

Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to enhance spinal fusion rates. Case reports of soft-tissue swelling, ectopic bone formation, and osteolysis have recently surfaced. It is hypothesized that incorporation of rhBMP-2 within a calcium phosphate (CaP) coating may help to localize delivery and mitigate these complications.

Purpose

To compare the characteristics of posterolateral fusion between rabbits receiving rhBMP-2 delivered via physical adsorption to a collagen sponge or rhBMP-2 incorporated within the physical structure of a CaP coating on a collagen sponge.

Study design/setting

New Zealand white rabbit model of posterolateral lumbar fusion at L5–L6.

Methods

Eighteen (18) New Zealand white rabbits underwent posterolateral spinal fusion at L5–L6. Rabbits received bilateral collagen sponges that were either coated with CaP (n=3), coated with CaP and dipped in rhBMP-2 (n=3), coated with a hybrid CaP–rhBMP-2 film (n=6), or coated with a hybrid CaP-rhBMP-2 film and dipped in rhBMP-2 (n=6). Animals were followed weekly with radiographs and were sacrificed at 6 weeks. Fusion masses were further characterized by manual palpation, computed tomography, and histology.

Results

Radiographic evaluation showed that animals in Group 3 (incorporated BMP) fused at 4 weeks, whereas animals in Group 2 (adsorbed BMP) and Group 4 (incorporated and adsorbed BMP) fused by 6 weeks. Animals that received rhBMP-2 physically adsorbed to the collagen sponge showed extension of the fusion mass beyond the L5–L6 level in 56% of cases and bone resorption in 78%. Histology of fusion masses showed mature bone formation in animals belonging to Groups 2, 3, and 4 and extensive osteoclast recruitment in animals belonging to Groups 2 and 4.

Conclusions

Delivery of rhBMP-2 via incorporation within CaP coatings results in increased rates of radiographic fusion. The burst release profile of rhBMP-2 adsorbed to surfaces, although effective in achieving fusion, may result in increased osteoclast recruitment.

Keywords: rhBMP-2, Bone graft substitute, Drug delivery, Animal model, Calcium phosphate